Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Random gene activation helps ulcer bug escape immune system

22.11.2004


The bacterium that causes ulcers and contributes to stomach cancers uses a clever interaction between two genes to randomly tighten and loosen its grip on the stomach, according to a study by researchers at Washington University School of Medicine in St. Louis and Umeå University in Sweden.



Helicobacter pylori often binds tightly to cells of the stomach lining to feed, but the newly identified interaction ensures that a small reservoir of bacteria are always more loosely connected. This reservoir is much more likely to survive if the host mounts a strong immune response. "Basically, if you’re holding onto someone’s T-shirt and they start punching you hard, you’d like to be able to let go," jokes Douglas Berg, Ph.D., Alumni Professor of Molecular Microbiology and an author of the study. "Any savvy bacteria are going to want to be able to do the same."

New insights into how H. pylori sticks to and then releases from the stomach wall will advance efforts to design better drugs and vaccines against the bacterium, which is estimated to be present in more than half of the world’s population. Most H. pylori infections in the U.S. and other industrialized nations can be treated with antibiotics, but treatments are too costly for many sufferers in underdeveloped nations, where the bacteria’s pervasiveness and poor sanitation significantly increase the risk of repeat infections. In addition, resistance to standard drug therapies is a major problem in these countries.


The study appears in the online edition of Proceedings of the National Academy of Sciences. It will appear in print in the journal on November 30. Researchers at Umeå University led by Anna Arnqvist, Ph.D., associate professor of molecular biology and medical biochemistry and a former Washington University predoctoral student, studied a Swedish strain of H. pylori. They focused on BabA, a protein that binds to Lewis B antigen receptor, a carbohydrate structure on the surface of stomach cells. Because they help organisms stick to particular targets in a glue-like fashion, BabA and proteins like it are collectively known as adhesins.

One of the Swedish strain’s two copies of the gene for BabA is "silent," or blocked from use by damage in a region of DNA normally involved in the gene’s activation. The second copy is missing an essential portion of DNA, making it completely nonfunctional. "This suggested that the strain doesn’t make BabA protein at all, making it equivalent in that regard to about one-third of all the other clinical isolates of H. pylori scientists have studied," Berg says.

Given that the strain didn’t appear to produce BabA protein, the bacteria should have been unable to get a grip on the Lewis B receptor. However, scientists found that a small minority of the bacteria still stuck very tightly to Lewis B.

Researchers then determined that this resulted from the bacteria recombining DNA from the silent BabA gene and DNA from the gene for a similar protein, BabB. Scientists aren’t sure what, if anything, BabB sticks to, but they do know that its similarities to BabA include biochemical "hooks" at the beginning and end of the protein. These hooks anchor the proteins in the bacteria’s cell wall. The BabA gene’s middle section encodes the glue that makes the protein stick. The rare bacteria that could grip Lewis B had spliced that middle section from the silent BabA gene into BabB, providing themselves with the equivalent of a working BabA gene and its protein product.

BabA-BabB gene recombination is relatively rare because characteristics of the segments of DNA being combined make them technically difficult for the bacteria to splice together. In addition, the BabB gene has a built-in genetic feature that allows the gene to turn on and off irregularly as the bacteria reproduce. "The BabB gene has a highly repetitive section that has a tendency to slip when the bacteria copies its DNA prior to cell division," Berg explains. "These slips can introduce extra repeats or delete them, shifting how the gene is translated from DNA to protein in a way that’s likely to halt protein synthesis by introducing a premature stop signal."

The net result, according to Berg, is that the bacteria’s ability to stick to the Lewis B receptor is metastable--in every generation, a small number of the new bacteria will switch from a tight grip to no grip, or vice-versa. "This metastability is likely an important component of the bacteria’s ability to adapt to host immune system responses," Berg says.

Berg and his Swedish colleagues are currently working to better understand BabB, investigating, among other things, whether the gene has a role to play on its own as a producer of a bacterial adhesin or only acts as a random enabler of BabA. Among the approximately 30 H. pylori surface proteins so far known to scientists, researchers have found other pairs of closely related genes. Included in these pairs are other genes that code for surface adhesins. "We also will take a close look at some of these pairs," Berg says. "We’re eager to find out whether they contain variations of this special regulatory system in BabA and BabB, or whether they control the strength and specificity of H. pylori adherence in other ways."

Michael C. Purdy | EurekAlert!
Further information:
http://www.wustl.edu

More articles from Life Sciences:

nachricht 'Y' a protein unicorn might matter in glaucoma
23.10.2017 | Georgia Institute of Technology

nachricht Microfluidics probe 'cholesterol' of the oil industry
23.10.2017 | Rice University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Salmonella as a tumour medication

HZI researchers developed a bacterial strain that can be used in cancer therapy

Salmonellae are dangerous pathogens that enter the body via contaminated food and can cause severe infections. But these bacteria are also known to target...

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

3rd Symposium on Driving Simulation

23.10.2017 | Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

 
Latest News

Microfluidics probe 'cholesterol' of the oil industry

23.10.2017 | Life Sciences

Gamma rays will reach beyond the limits of light

23.10.2017 | Physics and Astronomy

The end of pneumonia? New vaccine offers hope

23.10.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>